Classical cannabinoids such as the marijuana derived cannabinoid Δ9-tetrahydrocannabinol, (Δ9-THC) produce their pharmacological effects through interaction with specific cannabinoid receptors in the body. So far, two cannabinoid receptors have been characterized: CB1, a central receptor found in the mammalian brain and peripheral tissues and CB2, a peripheral receptor found only in the peripheral tissues. Compounds that are agonists or antagonists for one or both of these receptors have been shown to provide a variety of pharmacological effects. See, for example, Pertwee, R. G., Pharmacology of cannabinoid CB1 and CB2 receptors, Pharmacol. Ther., (1997) 74:129–180 and Di Marzo, V., Melck, D., Bisogno, T., DePetrocellis, L., Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action, Trends Neurosci. (1998) 21:521–528.
There is considerable interest in developing cannabinoid analogs possessing high affinity for the CB2 receptor. Cannabinoid analogs that preferentially stimulate the CB2 receptor, directly or indirectly, can provide clinically useful effects without affecting the subject's central nervous system. Such analogs may offer a rational therapeutic approach to a variety of disease states.